Cancer remains a major public health challenge despite progress in detection and therapy. Amongst the various types of cancer, LC is a frequent cancer in the Western world and among the most frequent causes of cancer-related mortality. It is the most common cause of cancer-related deaths among both men and women in the USA. It is predominantly a disease of the elderly: incidence increases with age, reaching 482/100,000 men>65 years, and peaks at age 75, reaching about 502/100,000 men. A man aged 65 has a 50 times greater risk of developing lung cancer than a man aged 25, and a 3 to 4 times greater risk than men aged 45 to 64.
About 90% of lung cancer cases in men and 80% in women are attributable to cigarette smoking. The risk of lung cancer is related to the total years of smoking, which exposes smokers to carcinogens and promoting agents. Risk also increases in the elderly because of the age-related decline in cellular DNA repair. From initial exposure to cigarette smoke to clinical presentation, lung cancer probably has a 15- to 20-year natural history.
The majority of LC tumors can be divided into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), which again is grouped into three major histological tumor types, i.e., squamous cell carcinoma, adenocarcinoma and large cell carcinoma.
SCLC accounts for about 20-25% of all lung cancer cases. SCLC is an aggressive neuroendocrine type of LC and has a very poor prognosis even if detected in early stages. SCLC is rarely amenable to curative treatment by resection. Because of the speed with which the disease progresses, SCLC is generally categorized using only two stages, i.e., limited and extensive disease, rather than the more complex TNM staging system (see below).
About 75-80% of LC cases are grouped into the class of NSCLC including squamous cell carcinoma (carcinoma=CA), adeno CA (comprising the subclasses of acinar CA, papillary CA, bronchoalveolar tumor, solid tumor, and mixed subtypes), and large cell carcinoma (comprising the subclasses of giant cell tumors, clear cell CA, adenosquamous CA, and undifferentiated CA).
NSCLC, if detected at late stages, has a very poor prognosis. The staging of cancer is the classification of the disease in terms of extent, progression, cell type and tumor grade. It groups cancer patients so that generalizations can be made about prognosis and the choice of therapy.
Today, the TNM system is the most widely used classification system based on the anatomical extent of cancer. It represents an internationally accepted, uniform staging system. There are three basic variables: T (the extent of the primary tumor), N (the status of regional lymph nodes) and M (the presence or absence of distant metastases). The TNM criteria are published by the UICC (International Union Against Cancer) (Sobin, L. H. and Fleming, I. D., TNM Classification of Malignant Tumors, Fifth Edition (1997), pp. 1803-1804.
Surgical resection of the primary tumor is widely accepted as the treatment of choice for early stage NSCLC. With the progression of NSCLC and, more specifically, the transition from stage IIIa (T3N1M0, T1N2M0, T2N2M0, T3N2M0) to IIIb (T4N0M0, T4N1M0, T4N2M0), a significant shift in the physician's approach is precipitated. However, if the cancer is detected during the more early stages (Ia-IIIa; preferably up to stage T3N1M0), the five-year survival rate varies between 35% and 80%. Detection at stage Ia ((T1N0M0); small tumor size, no metastasis) has evidently the best prognosis with a five-year survival of up to 80%.
Surgery is rarely, if ever, used in the management of stage IIIb-IV of NSCLC. Stage IV corresponds to distant metastasis, i.e., spread of the disease beyond the lungs and regional lymph nodes. The five-year survival rate in the later stages III and IV drops to between less than 15% and 1%, respectively.
What is especially important is that early diagnosis of NSCLC translates to a much better prognosis. Patients diagnosed as early as in stage Ia (T1N0M0), Ib (T2N0M0), IIa (T1N1M0), IIb, (T3N0M0), and IIIa (T3N1M0), if treated properly have an up to 80% chance of survival 5 years after diagnosis. This has to be compared to a 5-years survival rate of less than 1% for patients diagnosed once distant metastases are already present.
The earlier LC is diagnosed the better the chances of long term survival.
As mentioned above, the pathologist groups lung cancer into four major histological patterns, i.e., squamous cell carcinoma, adenocarcinoma, large cell carcinoma (altogether=NSCLC), and small cell carcinoma. However, what is quite important to note: often, two or more of these patterns occur simultaneously and histological grouping is extremely dependent on the skills of the pathologist in charge.
Additional means that could help in a more reproducible grouping of various types of lung cancer are urgently needed. Especially a marker indicative for SCC within the group of NSCLC tumors would be represent an important tool to aid such diagnosis.
It has surprisingly been found that the marker serpin B 13 represents an excellent tool to assess lung cancer. Using the marker serpin B 13 it is for example possible to differentiate squamous cell carcinoma from other histological types of lung cancer, e.g., adenocarcinoma.